Pathogenesis and biomarkers in ANCA-associated vasculitis

Abstract

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of systemic autoimmune diseases associated with serum ANCA positivity that affect small to medium vessels with inflammation and endothelial injury. This group includes several diseases: granulomatosis with polyangiitis (GPA), microscopic polyangiitis, eosinophilic GPA, and drug-induced AAV. A few AAVs are ANCA negative, but this form has decreased with the increase in detection methods. Different genetic, epigenetic, and environmental risk factors contribute to the pathogenesis of AAV. ANCA's role in the origin of vasculitis has led to a better grasp of the disease. Research has also improved the treatment, more precisely to tune its intensity, translating into better outcomes. However, there is still a gap to be filled with new potential and testable biomarkers for diagnosis, disease activity, and prognosis, which we discuss here.

New Biomarkers for Systemic Necrotizing Vasculitides

“…As emphasized above, SNV is a group of relapsing diseases, typically affecting small to medium vessels, with potential multiorgan involvement and characterized by necrotizing inflammation and endothelial injury [20]. At the beginning of our paper, we mentioned biomarkers associated with SNV and how they relate to one another.…”

“…The atypical ANCA pattern (A-ANCA) has been described in other autoimmune diseases, as well as in drug-induced AAV, and its role has not yet been revealed [19]. The recognition of the two main target autoantigens of ANCA, MPO and PR3, identified ANCA-positive disease subtypes but with distinctions in clinical phenotype, genetic basis, histological findings, epidemiology and response to therapy [20]. As mentioned, IIF of ethanol-fixated neutrophils and ELISA for antigen specificity are the main assays for detecting ANCAs.…”

“…Two important biomarkers of endothelial injury were studied in AAV: endothelial microparticles (EMPs) and circulating detached mature endothelial cells (CECs). Research on EMPs identified a positive correlation with disease activity compared to patients in remission [20].…”

“…Renal biopsy is essential for diagnosing IgAV-N, probably guiding treatment and predicting outcome; the procedure cannot be used repeatedly during patient follow-up [31]. In patients with active AAV, there were significantly higher urinary levels of Bb, C3a, C5a, and soluble C5b-9 [20].…”

“…In contrast, patients with low affinity would likely have lower vasculitic activity even though they may have higher serum levels of MPO-ANCA [67]. Studies have shown a better response to rituximab treatment in PR3-ANCA-positive patients in comparison to conventional therapy for induction and maintenance of remission with cyclophosphamide or azathioprine [20]. Hogan et al investigated the correlation between lung involvement and the substantial predictive value of PR3-ANCA for disease relapse [61].…”